CA2601687A1 - Combinaison pharmaceutique d'inhibiteurs de bcr-abl et de raf - Google Patents

Combinaison pharmaceutique d'inhibiteurs de bcr-abl et de raf Download PDF

Info

Publication number: CA2601687A1
Authority: CA; Canada
Prior art keywords: phenyl; substituted; lower alkyl; unsubstituted; amino
Prior art date: 2005-02-25
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA002601687A

Other languages

English (en)

Inventor

Paul W. Manley

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Novartis AG

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2005-02-25

Filing date

2006-02-24

Publication date

2006-08-31

2006-02-24 Application filed by Individual filed Critical Individual

2006-08-31 Publication of CA2601687A1 publication Critical patent/CA2601687A1/fr

Status Abandoned legal-status Critical Current

Links

239000003112 inhibitor Substances 0.000 title claims description 14
WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims abstract description 46
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201000010099 disease Diseases 0.000 claims abstract description 30
230000002062 proliferating effect Effects 0.000 claims abstract description 18
238000000034 method Methods 0.000 claims abstract description 17
229940123690 Raf kinase inhibitor Drugs 0.000 claims abstract description 6
102000051624 phosphatidylethanolamine binding protein Human genes 0.000 claims abstract description 6
108700021017 phosphatidylethanolamine binding protein Proteins 0.000 claims abstract description 6
239000003795 chemical substances by application Substances 0.000 claims description 20
238000011282 treatment Methods 0.000 claims description 14
206010035226 Plasma cell myeloma Diseases 0.000 claims description 10
201000000050 myeloid neoplasm Diseases 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 4
238000011260 co-administration Methods 0.000 claims description 3
PSYDCPHNVFLHOA-UHFFFAOYSA-N n-(2-tert-butylpyrimidin-5-yl)-4-isoquinolin-7-ylisoquinolin-1-amine Chemical compound C1=NC(C(C)(C)C)=NC=C1NC(C1=CC=CC=C11)=NC=C1C1=CC=C(C=CN=C2)C2=C1 PSYDCPHNVFLHOA-UHFFFAOYSA-N 0.000 claims description 3
XJGOPYWCSIEHLX-UHFFFAOYSA-N n-(4-tert-butylphenyl)-4-(pyridin-4-ylmethyl)isoquinolin-1-amine Chemical group C1=CC(C(C)(C)C)=CC=C1NC(C1=CC=CC=C11)=NC=C1CC1=CC=NC=C1 XJGOPYWCSIEHLX-UHFFFAOYSA-N 0.000 claims description 3
ATLZEZGQPAJHJZ-UHFFFAOYSA-N n-(4-tert-butylphenyl)-4-quinazolin-6-ylisoquinolin-1-amine Chemical compound C1=CC(C(C)(C)C)=CC=C1NC(C1=CC=CC=C11)=NC=C1C1=CC=C(N=CN=C2)C2=C1 ATLZEZGQPAJHJZ-UHFFFAOYSA-N 0.000 claims description 3
HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 claims description 3
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-1 as defined below Chemical class 0.000 description 106
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125000003282 alkyl amino group Chemical group 0.000 description 17
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ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
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NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 6
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125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
210000004214 philadelphia chromosome Anatomy 0.000 description 1
ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
125000005936 piperidyl group Chemical group 0.000 description 1
210000004180 plasmocyte Anatomy 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
HLIBNTOXKQCYMV-UHFFFAOYSA-N propylsulfamic acid Chemical compound CCCNS(O)(=O)=O HLIBNTOXKQCYMV-UHFFFAOYSA-N 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000003072 pyrazolidinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
238000002271 resection Methods 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000028327 secretion Effects 0.000 description 1
230000008054 signal transmission Effects 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012453 solvate Substances 0.000 description 1
210000000130 stem cell Anatomy 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
239000007940 sugar coated tablet Substances 0.000 description 1
238000009495 sugar coating Methods 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid group Chemical class S(N)(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
125000000542 sulfonic acid group Chemical group 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
230000008685 targeting Effects 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000010998 test method Methods 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
125000003396 thiol group Chemical class [H]S* 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
201000005112 urinary bladder cancer Diseases 0.000 description 1
210000001215 vagina Anatomy 0.000 description 1
125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA002601687A 2005-02-25 2006-02-24 Combinaison pharmaceutique d'inhibiteurs de bcr-abl et de raf Abandoned CA2601687A1 (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US65634005P	2005-02-25	2005-02-25
US60/656,340		2005-02-25
PCT/EP2006/001740 WO2006089781A1 (fr)	2005-02-25	2006-02-24	Combinaison pharmaceutique d'inhibiteurs de bcr-abl et de raf

Publications (1)

Publication Number	Publication Date
CA2601687A1 true CA2601687A1 (fr)	2006-08-31

Family

ID=36168564

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002601687A Abandoned CA2601687A1 (fr)	2005-02-25	2006-02-24	Combinaison pharmaceutique d'inhibiteurs de bcr-abl et de raf

Country Status (9)

Country	Link
US (1)	US20080207658A1 (fr)
EP (1)	EP1863491A1 (fr)
KR (1)	KR20070106036A (fr)
CN (1)	CN101160131A (fr)
AU (1)	AU2006218020A1 (fr)
CA (1)	CA2601687A1 (fr)
MX (1)	MX2007011866A (fr)
RU (1)	RU2007135284A (fr)
WO (1)	WO2006089781A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1923053A1 (fr) *	2006-09-27	2008-05-21	Novartis AG	Composition pharmaceutique comprenant de la nilotinib ou son sel
US8242271B2 (en)	2007-06-04	2012-08-14	Avila Therapeutics, Inc.	Heterocyclic compounds and uses thereof

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE459616T1 (de) *	1998-08-11	2010-03-15	Novartis Ag	Isochinoline derivate mit angiogenesis-hemmender wirkung
CA2443950C (fr) *	2001-04-20	2011-10-18	Bayer Corporation	Inhibition de la kinase raf a l'aide d'urees de quinolyl, d'isoquinolyl ou de pyridyl
GB0215676D0 (en) *	2002-07-05	2002-08-14	Novartis Ag	Organic compounds
ATE421324T1 (de) *	2003-03-11	2009-02-15	Novartis Ag	Verwendung von isochinolin-derivaten zur behandlung von krebs und erkrankungen im zusammenhang mit map kinase
JP2006525962A (ja) *	2003-04-14	2006-11-16	ノバルティスアクチエンゲゼルシャフト	増殖性疾患を処置するためのおよび増殖性疾患の処置の効果をモニタリングするための方法
AU2004246800B2 (en) *	2003-06-13	2008-12-04	Novartis Ag	2-aminopyrimidine derivatives as Raf kinase inhibitors
BRPI0414604A (pt) *	2003-09-23	2006-11-07	Novartis Ag	combinações de um inibiddor do receptor de vegf com outros agentes terapêuticos
AR045944A1 (es) *	2003-09-24	2005-11-16	Novartis Ag	Derivados de isoquinolina 1.4-disustituidas

2006
- 2006-02-24 CN CNA2006800126516A patent/CN101160131A/zh active Pending
- 2006-02-24 MX MX2007011866A patent/MX2007011866A/es unknown
- 2006-02-24 US US11/909,013 patent/US20080207658A1/en not_active Abandoned
- 2006-02-24 AU AU2006218020A patent/AU2006218020A1/en not_active Abandoned
- 2006-02-24 KR KR1020077021857A patent/KR20070106036A/ko not_active Withdrawn
- 2006-02-24 WO PCT/EP2006/001740 patent/WO2006089781A1/fr not_active Ceased
- 2006-02-24 EP EP06707271A patent/EP1863491A1/fr not_active Withdrawn
- 2006-02-24 RU RU2007135284/15A patent/RU2007135284A/ru unknown
- 2006-02-24 CA CA002601687A patent/CA2601687A1/fr not_active Abandoned

Also Published As

Publication number	Publication date
KR20070106036A (ko)	2007-10-31
EP1863491A1 (fr)	2007-12-12
AU2006218020A1 (en)	2006-08-31
RU2007135284A (ru)	2009-03-27
US20080207658A1 (en)	2008-08-28
MX2007011866A (es)	2007-10-10
WO2006089781A1 (fr)	2006-08-31
CN101160131A (zh)	2008-04-09

Legal Events

Date	Code	Title	Description
2011-02-24	FZDE	Discontinued

Publication	Publication Date	Title
US20080255171A1 (en)	2008-10-16	Combination of Nilotinib with Farnesyl Transferase Inhibitors
JP2013127001A (ja)	2013-06-27	ピリミジルアミノベンズアミド化合物であるタンパク質キナーゼ阻害剤および１７−ａａｇのようなｈｓｐ９０阻害剤を含む組合せ剤
US8653093B2 (en)	2014-02-18	Combination of pyrimidylaminobenzamide compounds and imatinib for treating or preventing proliferative diseases
CA2647803C (fr)	2014-05-27	Association comprenant un compose pyrimidylaminobenzamide et un inhibiteur de kinase thr315lle
US20080207658A1 (en)	2008-08-28	Pharmaceutical Combination of Bcr-Abl and Raf Inhibitors
WO2007051862A1 (fr)	2007-05-10	Combinaison de composés organiques
CA2615254C (fr)	2013-09-24	Combinaisons d'inhibiteurs de bcr-abl et d'inhibiteurs de mtor a base de pyrimidylaminobenzamide pour le traitement de la leucemie
AU2011202833B2 (en)	2012-05-24	Combination comprising a) a pyrimidylaminobenzamide compound, and b) a Thr315lle kinase inhibitor